TY - JOUR T1 - Analysis of Bone Samples from Patients with Spondyloarthritides—Identifying Causes of New Bone Formation in Axial Spondyloarthritis JF - The Journal of Rheumatology JO - J Rheumatol SP - 561 LP - 563 DO - 10.3899/jrheum.150046 VL - 42 IS - 4 AU - HEINER APPEL AU - JOACHIM SIEPER Y1 - 2015/04/01 UR - http://www.jrheum.org/content/42/4/561.abstract N2 - Ankylosing spondylitis (AS) is a chronic inflammatory disease predominantly affecting the axial skeleton, leading potentially to bone erosions, new bone formation, and ankylosis of the spine. The burden of disease is determined by the grade of acute inflammation causing pain and stiffness and by new bone formation causing a reduction in spinal mobility1.Histopathological studies from intervertebral discs2, femoral heads3,4, sacroiliac joints5,6, manubriosternal junction7, and zygapophyseal joints8,9,10 enabled us in the past to define characteristic histomorphological and immunohistochemical features of acute inflammation in bony samples from patients with AS: enthesitis and subchondral inflammation at the interface between bone and cartilage — subchondral osteitis — are the primary events in AS immunopathology. Cytokines such as tumor necrosis factor-α (TNF-α)5, interleukin 17 (IL-17)11, and IL-239 seem to be triggering factors during inflammatory processes. The rather unexpected observation that TNF-α blocking therapy did not reduce new bone formation and radiographic progression in patients with AS underscored the need for a better pathophysiological understanding of osteoproliferative mechanisms in AS.Currently, investigations are focused on 2 major hypotheses. The first is that new bone formation is an independent feature uncoupled from inflammation triggered by mechanical stress. Microdamage and/or cell stress at the enthesial site trigger both an inflammatory and an anabolic process in the bone, i.e., through bone morphogenic protein signaling, leading to typical clinical signs of AS12,13. The second is that new bone formation is closely linked to inflammation through initial … Address correspondence to Dr. H. Appel, Charité Universitätsmedizin Berlin, Campus Benjamin Franklin, Rheumatology, Hindenburgdamm 30, 12200 Berlin, Germany. E-mail: heiner.appel{at}charite.de ER -